A New wAy of
Understanding and Attacking Pancreatic Cancer
About IPI-926 About Pancreatic Cancer
IPI-926 is a potent, oral small molecule being The pancreas is a dual-function organ in the digestive and endocrine system. It is
developed by Infinity Pharmaceuticals. IPI- located deep within the abdomen, under the stomach, producing several important
926 inhibits Smoothened (or Smo), a key hormones, including insulin, and secreting pancreatic fluids that send digestive
component of the Hedgehog pathway. IPI- enzymes into the small intestine.
926 is currently being evaluated in the Phase
2 portion of an ongoing study in combination Pancreatic cancer is one of the most aggressive forms of cancer. More than 43,000
with gemcit abine (a chemotherapy) in people in the U.S. are diagnosed with pancreatic cancer each year. The lifetime
previously untreated patients with metastatic risk of having pancreatic cancer is about 1 in 71 and is the same for both men and
pancreatic cancer. Clinical activity was women. There are several risk factors that can increase a person’s chances of having
reported in a Phase 1b trial of IPI-926 in
pancreatic cancer, including smoking, obesity, age (most diagnosed patients are over
combination with gemcitabine in patients
55) and Type 2 diabetes 1.
with pancreatic cancer. Tumor regression
was obser ved in five out of 16 patients
Because pancreatic cancer is often diagnosed in the late stages of the disease,
evaluated, for a response rate of 31%. IPI-
effectively treating it is extremely difficult. Gemcitabine, a chemotherapy, is the
926 was well-tolerated in this study. The
current standard treatment for pancreatic cancer, but it still has one of the lowest
most commonly observed adverse events
were Grades 1 and 2 and included fatigue, survival rates of all major cancers. With a one-year relative survival rate of 25%
nausea and elevated transaminases. and a five-year rate of only 6% 1, there is a critical need for safe and more effective
treatments for patients with pancreatic cancer.
Targeting the Hedgehog pathway is a
fundamentally new approach to treating
pancreatic cancer. As there are no therapies In pancreatic cancer, tumor cells signal to surrounding
currently approved that target the Hedgehog stromal cells that support tumor growth and survival.
In preclinical models, inhibiting the Hedgehog pathway
pathway, IPI-926 has the potential to be first-
with IPI-926 depletes the stroma and increases the
in-class for the treatment of pancreatic cancer.
density of the blood vessels supporting the tumor,
making it easier for chemotherapy to reach the tumor
For more information about Infinity’s clinical cells. A Phase 2 study with IPI-926 and gemcitabine,
trial of IPI-926 in pancreatic cancer, please a chemotherapy, is now under way to test these
visit www.clinicaltrials.gov and enter the trial preclinical findings.
identifier “01130142” into the search box.
About Infinity Pharmaceuticals The Role of the “Hedgehog Pathway” in Pancreatic Cancer
Infinity is an innovative drug discovery and
The Hedgehog pathway is one that is normally active in embryonic development and
development company based in Cambridge,
regulates tissue and organ formation. Research has shown that in some cancers,
Massachusetts. Infinity’s goal is to discover,
the Hedgehog pathway is re-activated to support tumor growth and development.
develop, and deliver to patients best-in-class
Malignant activation of this pathway has been show to occur across a broad range of
medicines for difficult-to-treat diseases.
Infinity combines proven scientific expertise cancers, including pancreatic cancer. Recent studies have shown that inhibiting the
with a passion for developing novel small Hedgehog pathway may slow the progression and recurrence of cancer cell growth
molecule drugs that t arget emerging in certain cancers.
disease pathways.
Specifically, in pancreatic cancer, research suggests chemotherapy is unable to reach
pancreatic cancer tumors because they are protected by a stromal microenvironment,
which is dense and fibrous. Preclinical data published in Science 2 show that inhibiting
the Hedgehog pathway may change the tumor microenvironment – decreasing the
thickness of the stroma and allowing chemotherapy to reach the tumor more easily.
This finding is an important step forward that could help lead to new therapies for
For more information on Infinity,
pancreatic cancer.
please visit www.infi.com.
1
American Cancer Society, www.cancer.org 2
Olive, Kenneth P., et al. Inhibition of Hedgehog Signaling Enhances Delivery of
Chemotherapy in a Mouse Model of Pancreatic Cancer. Science 2009.
For more information about the clinical trial of IPI-926 in pancreatic cancer, please visit www.clinicaltrials.gov